Gene research to explain autistic savants

Mice lacking a certain brain protein learn some tasks better but also forget faster, as per new research from MIT that may explain the phenomenon of autistic savants in humans. The work could also result in future therapys for autism and other brain development disorders.

Scientists at the Picower Institute for Learning and Memory at MIT report in the Feb. 13 issue of the Journal of Neuroscience that mice genetically engineered to lack a key protein used for building synapses--the junctions through which brain cells communicate--actually learned a spatial memory task faster and better than normal mice. But when tested weeks later, they couldn't remember what they had learned as well as normal mice, and they had trouble remembering contexts that should have provoked fear.

"These opposite effects on different types of learning are reminiscent of the mixed features of autistic patients, who may be disabled in some cognitive areas but show enhanced abilities in others," said Albert Y. Hung, a postdoctoral associate at the Picower Institute, staff neurologist at Massachusetts General Hospital and co-author of the study. "The superior learning ability of these mutant mice in a specific realm is reminiscent of human autistic savants."

Autism is one of a group of developmental disabilities known as autism spectrum disorders (ASDs), in which a person's ability to communicate and interact with others is impaired. The Centers for Disease Control and Prevention estimate that one in 150 American children have an ASD. Occasionally, an autistic person has an outstanding skill, such as an incredible rote memory or musical ability. Such individuals--like the character Dustin Hoffman played in the film "Rain Man"--may be referred to as autistic savants.........

Hostility, Depression And Heart Disease

Scientists led by Jesse Stewart, Ph.D., assistant professor of psychology at Indiana University-Purdue University Indianapolis, report that hostility and depression appear to act together in a complex way to elevate inflammatory proteins in the human body, possibly putting hostility plus depression on the list of risk factors for heart disease along with high blood pressure, elevated cholesterol, and smoking.

The findings, that hostility enhances inflammatory processes relevant to heart disease only in the presence of depressive symptoms, are reported in the February-March 2008 issue of Psychosomatic Medicine. Dr. Stewart and his colleagues examined associations of depressive symptoms and hostility with blood levels of two inflammatory proteins, interleukin-6 and C-reactive protein, that are predictive of future heart disease. Participants in the study were 316 healthy men and women aged 50-70.

Prior studies have observed depression to be linked to raised inflammatory protein levels. Other studies have confirmed links between hostility and inflammatory proteins that are predictive of heart disease. But this study is the first to find that, among elderly adults, the relationship between hostility and these inflammatory proteins depends on the level of depression.........

Mechanism leading to cleft palate

Zebrafish face with cleft palate.

Credit: Courtesy of John Postlethwait

By creating a genetic mutation in zebrafish, University of Oregon scientists say they've discovered a previously unknown mechanism for cleft palate, a common birth defect in humans that has challenged medical professionals for centuries.

Many molecular pathways in zebrafish are present in humans and other vertebrates. By studying the induced mutation in zebrafish, the 10-member research team isolated a disruption in early developmental signaling involving Pdgf, a platelet-derived growth-factor protein, and a microRNA known as Mirn140, the researchers write in a paper posted online in advance of regular publication the monthly journal Nature Genetics.

Mutant zebrafish lacking Pdgf had cleft palate similar to many human babies, showing that this growth factor helps to organize cells that make the palate. It came as a surprise that zebrafish into which the scientists had injected too much Mirn140 also had cleft palate.

MicroRNAs are small gene products, found to be involved in gene expression, that were first described in 1993 by researchers at Harvard University. The term microRNA was introduced in when these single-strand RNA molecules about nucleotides in length were more fully detailed in Science in October 2001 by Gary Ruvkun of Massachusetts General Hospital in Boston.........

Moss protein plays role in Alzheimer's Disease

A twenty-eight-day old Physcomitrella (left) moss gametophyte has a surprising link to an amyloid plaque, (right) found in brains that have Alzheimer's disease.

Preventing Alzheimer's disease is a goal of Raphael Kopan, Ph.D., professor of molecular biology and pharmacology at the Washington University School of Medicine. The moss plant Physcomitrella patens studied in the laboratory of Ralph S. Quatrano, Ph.D., the Spencer T. Olin Professor and chair of the biology department on WUSTL's Danforth Campus, might inch Kopan toward that goal. Here's how.

The gene presenilin (PS) in mammals provides the catalytic activity for an enzyme called gamma secretase, which cleaves, or cuts, important proteins Notch, Erb4 and the amyloid precursor protein (APP), all key components of communication channels that cells use to arbitrate functions during development. There are two mammalian genes that occur in mammals for which mutations cause an earlier onset of Alzheimer's. One is APP, where a fragment of the protein accumulates in amyloid plaques linked to the disease. Another common site for mutations is found in PS proteins. The enzyme gamma secretase contains PS and works to dispose of proteins stuck in the cellular membrane.

This enzyme, with PS at its core, mediates two cellular decisions. One is to cut APP and, as a byproduct, generate the bad peptide linked to Alzheimer's; the other is to cut the Notch protein in response to specific stimuli. Notch is then free to enter the nucleus of cells where it partakes in regulating normal gene expression. Without Notch activity, a mammal has no chance of living.........

High School to the First Year of College

Increases in young women's drinking during the transition from high school through the first year of college can have dangerous physical, sexual and psychological implications, as per a report out of the University at Buffalo's Research Institute on Addictions.

The good news is that during the first year of college, when a number of young women increase their drinking, the majority (78 percent) of the 870 incoming freshmen women who took part in the study did not experience any victimization. The bad news, however, is that among the 22 percent of women who were victimized, 13 percent experienced severe physical victimization and 38 percent experienced severe sexual victimization.

The research results were reported in the January 2008 issue of the prestigious Journal of Studies on Alcohol and Drugs.

"This is the first study that we know of that has compared risk for physical and sexual assault among college women based on changes in drinking during this transition period," said Kathleen A. Parks, Ph.D., principal investigator on the study. "Clearly, abstaining from drinking is a protective measure. However, young college women should be aware that becoming a new drinker or increasing one's drinking during this transition increases the likelihood of victimization."........

Smart pillbox could be a lifesaver

An MIT student and collaborators have designed the uBox, a 'smart' pillbox that dispenses pills, alerts the patient that it's time to take the medication, records the time the pill was taken and prevents double-dosing. Image courtesy / Manish Bhardwaj

In The World is a new column that explores the ways people from MIT are using technology--from the appropriately simple to the cutting edge--to help meet the needs of local people in places around the planet. If you know of a good example and would like the News Office to write about it, please e-mail dlc1@mit.edu.

Tuberculosis has long been eradicated from the world's industrialized nations but continues to take a terrible toll in a few poor, rural regions of Asia and Africa. Every year, 10 million new cases are diagnosed and two million people die of the disease.

It's not that new therapys are needed--medical science long ago figured out how to cure tuberculosis using a cocktail of antibiotics. The problem is getting the medicine to the people who need it and, most difficult, making sure they follow the six-month regimen of daily doses.

Failure to follow the regimen not only leads to likely death of that patient, but fosters the development of antibiotic-resistant strains of the disease. "The problem is, how do you get people to take this complex regimen," says Manish Bhardwaj, a doctoral student in the Department of Electrical Engineering and Computer Science who works in the Microsystems Technology Laboratories.

After a year of hard work and about eight revisions, Bhardwaj and a team of collaborators think they may have found the answer. It's a high-tech solution in a simple, inexpensive and easy-to-use -package.........

Why certain ovarian cancers develop resistance

A team of scientists led by Fred Hutchinson Cancer Research Center has identified a new mechanism that explains why some recurrent ovarian tumors become resistant to therapy with usually used platinum-based chemotherapy drugs such as cisplatin and carboplatin. They describe their research online Feb. 10 in the journal Nature.

While these findings are based on the study of ovarian-cancer cells from women with inherited mutations in the BRCA2 gene, they also may help explain the mechanics of cisplatin resistance in ovarian-cancer patients with BRCA1-gene mutations. Together such genetic mistakes are thought to cause about 10 percent of ovary cancers, as per senior author Toshiyasu (Toshi) Taniguchi, M.D., Ph.D.

Because BRCA1 and BRCA2 have similar functions in terms of DNA repair, we may be able to generalize these findings for women with either mutation, said Taniguchi, an assistant member of the Hutchinson Centers Human Biology and Public Health Sciences divisions.

BRCA2 works to repair damaged DNA; inherited mutations in this gene disrupt that ability, which increases the risk of ovarian and breast cancer. At the same time, such mutations also make cancer cells more vulnerable to DNA-damaging agents such as cisplatin and carboplatin. While ovarian tumors initially respond very well to platinum-based chemotherapy, eventually between 70 percent and 80 percent of advanced-stage ovarian-cancer patients develop a resistance to these drugs.........

Artificial sweeteners linked to weight gain

Want to lose weight" It might help to pour that diet soda down the drain. Scientists have laboratory evidence that the widespread use of no-calorie sweeteners may actually make it harder for people to control their intake and body weight. The findings are reported in the recent issue of Behavioral Neuroscience, which is published by the American Psychological Association (APA).

Psychology experts at Purdue Universitys Ingestive Behavior Research Center reported that relative to rats that ate yogurt sweetened with glucose (a simple sugar with 15 calories/teaspoon, the same as table sugar), rats given yogurt sweetened with zero-calorie saccharin later consumed more calories, gained more weight, put on more body fat, and didnt make up for it by cutting back later, all at levels of statistical significance.

Authors Susan Swithers, PhD, and Terry Davidson, PhD, surmised that by breaking the correlation between a sweet sensation and high-calorie food, the use of saccharin changes the bodys ability to regulate intake. That change depends on experience. Problems with self-regulation might explain in part why obesity has risen in parallel with the use of artificial sweeteners. It also might explain why, says Swithers, scientific consensus on human use of artificial sweeteners is inconclusive, with various studies finding evidence of weight loss, weight gain or little effect. Because people may have different experiences with artificial and natural sweeteners, human studies that dont take into account previous consumption may produce a variety of outcomes.........

Effort To Sequence 1,000 Human Genomes

Washington University School of Medicine in St. Louis will play a leading role in an international collaboration to sequence the genomes of 1,000 individuals. The ambitious 1000 Genomes Project will create the most detailed picture to date of human genetic variation and likely will identify a number of genetic factors underlying common diseases.

Drawing on the expertise of research teams in the United States, China and England, the project will develop a new map of the human genome that will provide a close-up view of medically relevant DNA variations at a resolution unmatched by current technology. As with other major human genome reference projects, data from the 1000 Genomes Project will be made swiftly available to the worldwide scientific community through free public databases.

"A project like this would have been unimaginable only a few years ago," says Elaine Mardis, Ph.D., co-director of the University's Genome Sequencing Center, and one of the project's lead investigators. "We now have the ability to examine in intimate detail variations in the genetic code that differ from person to person."

At the genetic level, any two humans are more than 99 percent alike. However, it is important to understand the small fraction of genetic material that varies among people because it can help explain differences in individuals' risk of disease, response to drugs or reaction to environmental factors. Common variation in the human genome is organized into local neighborhoods called haplotypes, which commonly are inherited as intact blocks of information.........

PET Outperforms CT In Malignant Lung Nodules

Scientists involved in a large, multi-institutional study comparing the accuracy of positron emission tomography (PET) and computed tomography (CT) in the characterization of lung nodules observed that PET was far more reliable in detecting whether or not a nodule was cancerous.

"CT and PET have been widely used to characterize solitary pulmonary nodules (SPNs) as non-malignant or cancerous," said James W. Fletcher, professor of radiology at Indiana University School of Medicine in Indianapolis, Ind. "Almost all prior studies examining the accuracy of CT for characterizing lung nodules, however, were performed more than 15 years ago with outdated technology and methods, and prior PET studies were limited by small sample sizes," he noted.

"Detecting and characterizing SPNs is important because cancerous nodules represent a potentially curable form of lung cancer. Identifying which SPNs are most likely to be cancerous enables physicians to initiate the proper treatment before local or distant metastases develop," said Fletcher.

In a head-to-head study addressing the limitations of prior studies, PET and CT images on 344 patients were independently interpreted by a panel of experts in each imaging modality, and their determination of non-malignant and cancerous nodules were in comparison to pathologic findings or changes in SPN size over the next two years.........

Did you know?Studies in monkeys and women suggest that unlike traditional estrogen therapy, a diet high in the natural plant estrogens found in soy does not increase the risk of uterine cancer in postmenopausal women, according to Mark Cline, D.V.M., Ph.D., an associate professor of comparative medicine at Wake Forest University Baptist Medical Center.